Nonglycosylated fibronectin, from tunicamycin-treated chicken embryo fibroblasts, was degraded more rapidly to acid-soluble products than glycosylated fibronectin by pronase, thermolysin, trypsin and chymotrypsin. The absence of carbohydrate did not markedly affect overall patterns of proteolytic fragments identified by SDS-PAGE. Except for the expected increases in electrophoretic mobilities of the nonglycosylated peptides, the only important difference was that the nonglycosylated fragment corresponding to the carbohydrate-rich, collagen-binding domain, was completely digested by the proteases in 60 min at 30 C. In contrast, the comparable fragment from glycosylated fibronectin was resistant to protease digestion. Heparin-binding domains that normally lack carbohydrate are equally susceptible to proteases in glycosylated nonglycosylated fibronectin. Similar results were obtained by comparison of nonglycosylated RNase A with glycosylated RNase B. Also "modified" RNaLc B, that had undergone partial removal of carbohydrate from the protein molecule, was degraded at a rate intermediate between that observed for fully glycosylated RNase B and nonglycosylated RNase A. Finally, when glycosylation of cellulr protein is inhibited, cathepsin B, a lysosomal protease, is secreted.